Tumors of the hematopoietic and lymphoid tissues or haematopoietic and lymphoid malignancies are tumors that affect the blood, bone marrow, lymph, and lymphatic system. As those elements are all intimately connected through both the circulatory system and the immune system, a disease affecting one will often affect the others as well, making myeloproliferation and lymphoproliferation (and thus the leukemias and the lymphomas) closely related and often overlapping problems.
Hematological malignancies may derive from either of the two major blood cell lineages: myeloid and lymphoid cell lines. The myeloid cell line normally produces granulocytes, erythrocytes, thrombocytes, macrophages and mast cells; the lymphoid cell line produces B, T, NK and plasma cells. Lymphomas, lymphocytic leukemias, and myeloma are from the lymphoid line, while acute and chronic myelogenous leukemia, myelodysplastic syndromes and myeloproliferative diseases are myeloid in origin.
B-cell lymphomas are types of lymphoma affecting B cells. Lymphomas are blood cancers in the lymph nodes. B-cell lymphomas include both Hodgkin's lymphomas and most non-Hodgkin lymphomas.
Follicular lymphoma (FL) is a type of blood cancer. It is the most common of the indolent (slow-growing) non-Hodgkin's lymphomas, and the second-most-common form of non-Hodgkin's lymphomas overall. It is defined as a lymphoma of follicle center B-cells (centrocytes and centroblasts), which has at least a partially follicular pattern.
B-cell chronic lymphocytic leukemia (B-CLL), also known as chronic lymphoid leukemia (CLL), is the most common type of leukemia (a type of cancer of the white blood cells) in adults. CLL affects B cell lymphocytes, which originate in the bone marrow, develop in the lymph nodes, and normally fight infection by producing antibodies. CLL is a stage of small lymphocytic lymphoma (SLL), a type of B-cell lymphoma, which presents primarily in the lymph nodes. CLL and SLL are considered the same underlying disease, just with different appearances.
Diffuse large B-cell lymphoma (DLBCL or DLBL) is a cancer of B cells, a type of white blood cell responsible for producing antibodies. Diffuse large B-cell lymphoma encompasses a biologically and clinically diverse set of diseases, many of which cannot be separated from one another by well-defined and widely accepted criteria.
B cell receptor (BCR) mediated signalling is required for chronic lymphocytic leukemia (CLL) pathogenesis and drugs which target kinases within the BCR signalling complex are revolutionising the treatment of this disease.
Some chemotherapeutic agents employed in CLL therapy include ibrutinib (Imbruvica®), which targets BTK, and idelalisib (Zydelig®), which targets PI3Kδ. However these compounds suppress the disease and are not typically curative. Additionally, CLL patients may develop resistance to these chemotherapeutic agents either via mutations in BTK or downstream signalling proteins, or other mechanisms. An additional resistance mechanism to chemotherapy in CLL may be via IL-4 mediated JAK/STAT signalling, which may protect against cytotoxic agents. Accordingly, there is a need for new therapies for hematological malignancies.